This is an application for a K23 award for Dr. Theodore Omachi, a pulmonologist at the University of California, San Francisco (UCSF). Dr. Omachi is establishing himself as a patient-oriented clinical investigator of the overlap syndrome of chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA). Although the pathophysiology of COPD and OSA suggests that these two diseases may be particularly harmful in combination, the effects of the COPD-OSA overlap syndrome on health outcomes have not been elucidated. Dr. Omachi will leverage the existing infrastructure of his primary mentor's currently-funded NHLBI R01, which is following 1,202 COPD subjects recruited through Kaiser Permanente's integrated health system. These subjects have been carefully characterized with both survey-based and physiologic measurements. In planned subject reassessments, Dr. Omachi's proposed study will add controlled sleep studies as well as other objective and survey-based measures specific to the overlap syndrome. In Aim 1, Dr. Omachi will investigate the extent to which OSA contributes to poor health status, including reduced exercise tolerance and poor health-related quality of life, in COPD patients. In Aim 2, he will determine the prospective association of the overlap syndrome with adverse health outcomes, direct medical costs, and indirect work disability costs. In Aim 3, he will examine the impact of the COPD-OSA overlap syndrome on nocturnal hypoxemia, diurnal hypercapnia, systemic inflammation, daytime sleepiness, and sleep quality and will furthermore investigate the mediating role of these factors in contributing to poor health status and outcomes in the overlap syndrome. This K23 award will provide Dr. Omachi with the support necessary to: (1) become an expert patientoriented clinical researcher of the overlap syndrome of COPD and OSA, (2) develop skills specific to sleep medicine necessary both for the proposed research and his career as an independent investigator, (3) implement advanced biostatistical methods which incorporate translational medicine into clinical studies, (4) refine skills necessary to perform complex economic analyses, and (5) develop an independent clinical research career. To achieve these goals, Dr. Omachi has assembled a mentoring team comprised of a primary mentor, Dr. Mark Eisner, an expert in obstructive lung disease epidemiology, and 3 co-mentors: Dr. Paul Blanc, a renowned researcher of work disability; Dr. Edward Yelin, an expert in health economics; and Dr. Steven Gregorich, an expert in biostatistical analyses. His team also includes 4 scientific advisors: Dr. Samuel Kuna, who researches the ambulatory management of OSA; Dr. David Claman, Director of the UCSF Sleep Disorders Center; Dr. Patricia Katz, an expert in psychometric analyses; and Dr. Michael Matthay, an expert in pulmonary translational medicine techniques. This dedicated mentorship team, combined with a rigorous, supportive research environment, will ensure Dr. Omachi develops into a successful independent investigator.